Adequate blood supply to living tissue is a fundamental prerequisite for its proper functioning. This supply, however, is often impaired due to several acute and/or chronic diseases, for instance, mechanical obstruction or inflammation as a consequence of arteriosclerosis or diabetes. An impaired blood supply can damage tissue locally or systemically, causing generalized pathologies, or pathologies specific to the heart, brain, eye, etc. Many of these diseases are both progressive and treatable, especially if diagnosed in their early stages. Early detection is thus highly desirable, because it enables preventive treatment. The high incidence of pathological vascular alterations in the population, and the severe consequences of their later stages, makes early detection and treatment even more desirable.
Methods for assessing the internal condition of blood vessels should ideally be rapid, objective, quantitative, preferably continuous, and as non-invasive as possible. Most important, there is the need for a test, which can be simply performed as a screening test on a large population, and by personnel with minimal technical training, in a similar fashion to blood-pressure measurements. MRI and non-invasive ultrasound imaging techniques lack the spatial resolution necessary to detect the onset of arteriosclerotic deterioration of blood vessel walls. The current gold-standard for the detection of plaques is autoradiography or scintigraphy, by means of the targeted injection of radioactive substances by a catheter. However, these techniques are invasive, not totally risk-free and very demanding, requiring complicated technical equipment and skilled medical personnel. They cannot, therefore, be performed as a screening test on a large population and are usually reserved for patients already suffering from the consequences of arteriosclerosis. Indirect examination, such as chemical blood analysis for cholesterol, triglycerides, lipids, HDL and other substances can be performed on a large scale, but are only indicative.
Methods assessing the status of blood vessel walls have been described in “MR imaging of the vessel wall”, by H. H Quick., J. F. Debatin and M. E. Ladd, published in Eur. Radiol., Vol. 12(4), pp. 889-900 (Apr.2002), and are indicative of the effort invested in developing such techniques. With the exception of endoscopy and MRI, generally used techniques for determining the status of blood vessel walls rely on macroscopic changes, such as an impaired blood exchange rate, leakage, or impaired supply resulting from partial or total obstructions. Endoscopy does allows direct visualization of the interior of blood vessels, but is invasive, not risk-free, and requires skilled medical personnel. MRI, though generally non-invasive, suffers from low signal to noise ratio. Radio frequency (RF) coils have been developed to improve the signal, but some of the most effective of these are for intravascular use, thus rendering the technique invasive. Non-invasive surface coils are limited in application to large vessels near the body's surface—primarily the carotid and right coronary arteries. To detect the early development of plaque and to view it globally rather than locally, intravascular contrast agents on the basis of ultrasmall particles of iron oxide can be used as an MRI marker of macrophage activity within the plaque. Tolerance of the injected substance is not always acceptable, however. In all its modalities, MRI requires expensive apparatus.
The main limitations of the previously described in vivo techniques can be summarized as follows:    (i) they have intrinsically low spatial resolution, or for the case of metabolic indicators, such as blood tests, no spatial information at all;    (ii) they are indirect;    (iii) they are invasive;    (iv) they are limited to specific vessels; and    (v) they require expensive apparatus and/or highly trained technical and medical staff to be performed.
Furthermore, since the effect of disease on blood vessels may be heterogeneous across different compartments, data based on tests of the one-vessel-at-a-time type, as in endoscopy, may miss important diagnostic information which would be available from datasets having the character of an image. Also, due to the generally limited spatial resolution of the aforementioned techniques, arteriosclerosis can usually be detected only at a progressed stage, in the presence of large plaques, whereas early detection is highly desirable.
There thus exists a need for a new method and technique that can quantitatively assess the status of blood vessel walls. The method should preferably be non-invasive, should preferably not necessitate the use of overly expensive and complicated apparatus, and should not require complex know-how or advanced medical proficiency. In addition, the method should be able to assess the state of blood vessel walls for the different vascular compartments, including arteries, arterioles, capillaries, venules and veins, each of which may be affected differently by a given pathology. The method should be capable of detecting small blood vessels non-invasively at high-resolution.
The disclosures of the documents and publications mentioned in this section, and in the other sections of this application, are hereby incorporated by reference, each in its entirety.